Study On Synthesis Of α-trifluoromethyl-α-hydroxyl Weinreb Amides And α-trifluoromethylpropargyl Alcohols

Recently,Organofluorine compounds are widely found in pharmaceuticals,agrochemicals and materials and have been paid more and more attention,because the introduction of fluorine atoms leads to changes in the physical,chemical and biological properties of a compound.Among the different fluorinated functional groups,the trifluoromethyl group（CF₃）is highly valuable because as the incorporation of the trifluoromethyl group often improves the lipophilicity,metabolic stability of a compound,even its ability to penetrate the blood brain barrier.However,development of transformations to incorporate trifluoromethyl group is usually a great challenge due to its strong electron-withdrawing character.It is therefore apparent that the development of excellent trifiuormethylating reagents and efficient methods for trifluoromethylation become very important.This thesis includes the following four parts.Chapter1 Advances in application of trifluoromethylationThe application of trifluoromethylation in organic synthesis was summarized in this chapter.Chapter 2 Synthesis ofα-trifluoromethyl-α-hydroxyl Weinreb amidesIn this chapter,selective trifluoromethylation ofα-oxo-Weinreb amides wasexplored using trimethyl-（trifluoromethyl）silane as fluorinating reagent.A series ofα-trifluoromethyl-α-hydroxyl Weinreb amides were successfully synthesized in high yields and their reaction with organometallic reagents was investigated.Chapter 3“One-pot”synthesis ofα-trifluoromethylpropargyl alcohol mediated by magnesiumInthischapter,magnesium-mediatedone-potreactionsof trifluoromethylacetophenones,n-butyl bromide and phenylacetylene for the synthesis ofα-trifluoromethyl propargylic alcohols were investigated.A series ofα-trifluoromethyl Propargyl alcohol compounds were obtained in high yields.Our method has the following advantages:higher yields,milder reaction conditions and easy operation.